Genome-wide nucleosome positioning during embryonic stem cell development

Nat Struct Mol Biol. 2012 Nov;19(11):1185-92. doi: 10.1038/nsmb.2419. Epub 2012 Oct 21.

Abstract

We determined genome-wide nucleosome occupancies in mouse embryonic stem cells and their neural progenitor and embryonic fibroblast counterparts to assess features associated with nucleosome positioning during lineage commitment. Cell-type- and protein-specific binding preferences of transcription factors to sites with either low (Myc, Klf4 and Zfx) or high (Nanog, Oct4 and Sox2) nucleosome occupancy as well as complex patterns for CTCF were identified. Nucleosome-depleted regions around transcription start and transcription termination sites were broad and more pronounced for active genes, with distinct patterns for promoters classified according to CpG content or histone methylation marks. Throughout the genome, nucleosome occupancy was correlated with certain histone methylation or acetylation modifications. In addition, the average nucleosome repeat length increased during differentiation by 5-7 base pairs, with local variations for specific regions. Our results reveal regulatory mechanisms of cell differentiation that involve nucleosome repositioning.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology*
  • Chromatin Immunoprecipitation
  • DNA Methylation
  • Electrophoresis, Agar Gel
  • Embryonic Stem Cells / metabolism*
  • Embryonic Stem Cells / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • High-Throughput Nucleotide Sequencing
  • Histones / metabolism
  • Mice
  • Molecular Sequence Data
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Sequence Alignment
  • Transcription Factors / metabolism

Substances

  • Histones
  • Nucleosomes
  • Transcription Factors

Associated data

  • GEO/GSE40896